Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Accuracy of Cytologic vs Histologic Specimens for Assessment of Programmed Cell Death Ligand-1 Expression in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC). RESEARCH QUESTION: What is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC? STUDY DESIGN AND METHODS: The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models. RESULTS: Twenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively. INTERPRETATION: Cytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens. TRIAL REGISTRATION: PROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/.

Preoperative mediastinal staging in early-stage lung cancer: Targeted nodal sampling is not inferior to systematic nodal sampling.

OBJECTIVE: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05. RESULTS: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. CONCLUSIONS: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients.

Reduction of Chest Drain Overuse Through Implementation of a Pleural Drainage Order Set.

BACKGROUND AND OBJECTIVES: Small chest drains are used in many centers as the default drainage strategy for various pleural effusions. This can lead to drain overuse, which may be harmful. This study aimed to reduce chest drain overuse. METHODS: We studied consecutive pleural procedures performed in the radiology department before (August 1, 2015, to July 31, 2016) and after intervention (September 1, 2019, to January 31, 2020). Chest drains were deemed indicated or not based on criteria established by a local interdisciplinary work group. The intervention consisted of a pleural drainage order set embedded in electronic medical records. It included indications for chest drain insertion, prespecified drain sizes for each indication, fluid analyses, and postprocedure radiography orders. Overall chest drain use and proportion of nonindicated drains were the outcomes of interest. RESULTS: We reviewed a total of 288 procedures (pre-intervention) and 155 procedures (post-intervention) (thoracentesis and drains). Order-set implementation led to a reduction in drain use (86.5% vs 54.8% of all procedures, P < .001) and reduction in drain insertions in the absence of an indication (from 45.4% to 29.4% of drains, P = .01). The need for repeat procedures did not increase after order-set implementation (22.0% pre vs 17.7% post, P = .40). Complication rates and length of hospital stay did not differ significantly after the intervention. More pleural infections were treated with drain sizes of 12Fr and greater (31 vs 70%, P < .001) after order-set deployment, and direct procedural costs were reduced by 27 CAN$ per procedure. CONCLUSION: Implementation of a pleural drainage order-set reduced chest drain use, improved procedure selection according to clinical needs, and reduced direct procedural costs. In institutions where small chest drains are used as the default drainage strategy for pleural effusions, this order set can reduce chest drain overuse.

Reporting Standards for Diagnostic Testing: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Diagnostic testing is fundamental to medicine. However, studies of diagnostic testing in respiratory medicine vary significantly in terms of their methodology, definitions, and reporting of results. This has led to often conflicting or ambiguous results. To address this issue, a group of 20 respiratory journal editors worked to develop reporting standards for studies of diagnostic testing based on a rigorous methodology to guide authors, peer reviewers, and researchers when conducting studies of diagnostic testing in respiratory medicine. Four key areas are covered, including defining the reference standard of truth, measures of dichotomous test performance when used for dichotomous outcomes, measures of multichotomous test performance for dichotomous outcomes, and what constitutes a useful definition of diagnostic yield. The importance of using contingency tables for reporting results is addressed with examples from the literature. A practical checklist is provided as well for reporting studies of diagnostic testing.

Impact of a Pleural Care Program on the Management of Patients With Malignant Pleural Effusions.

BACKGROUND: Malignant pleural effusions (MPEs) are common and associated with a poor prognosis. Yet, many patients face suboptimal management characterized by repeated, nondefinitive therapeutic procedures and potentially avoidable hospital admissions. METHODS: We conducted a retrospective comparison of patients who underwent a definitive palliative intervention for MPE (indwelling pleural catheter or pleurodesis) at our center, before and after the implementation of a pleural care program. Targeted interventions included staff education, establishment of formal pleural drainage policies, a pleural clinic with weekday walk-in capacity, and a rapid access pathway for oncology patients. Outcomes assessed were the proportion of emergency room (ER) presentations, hospitalizations, number of nondefinitive pleural procedures, and time-to-definitive palliative procedure. RESULTS: A total of 144 patients were included: 69 in the preintervention group and 75 in the postintervention group. Although there was no difference in the proportion of ER presentations before and after interventions (43.5% vs. 38.7%, P =0.56), hospital admissions declined significantly (47.8% vs. 24.0%, P =0.003). The proportion of patients undergoing chest drain insertion decreased significantly (46.4% vs. 13.3%, P <0.001), with a stable low number of nondefinitive procedures per patient (1.6±1.1 vs. 1.3±0.9, P =0.32). A 7-day decrease in median time from presentation-to-definitive palliative procedure ( P =0.05) was observed. CONCLUSION: A targeted pleural care program improved MPE palliation through reduction in hospitalizations and chest drain use, and shorter time-to-definitive palliation, despite failing to reduce ER presentations.

Diagnostic Accuracy of Bronchoscopy Procedures: Definitions, Pearls, and Pitfalls.

The field of diagnostic bronchoscopy has developed at an accelerated pace. Certain limitations have plagued the evaluation of advanced bronchoscopy techniques, including the use of inconsistently defined measures of diagnostic accuracy, and confusion around the definition of "diagnostic yield." This methodological review outlines standard measures of diagnostic accuracy and highlights how these differ from "diagnostic yield." We draw examples from the interventional bronchoscopy literature to illustrate key concepts and potential pitfalls.

Smoking Cessation by Phone Counselling in a Lung Cancer Screening Program: A Retrospective Comparative Cohort Study.

Introduction: Smoking cessation integration within lung cancer screening programs is challenging. Currently, phone counselling is available across Canada for individuals referred by healthcare workers and by self-referral. We compared quit rates after phone counselling interventions between participants who self-refer, those referred by healthcare workers, and those referred by a lung cancer screening program. Methods: This is a retrospective cohort study of participants referred to provincial smoking cessation quit line in contemporaneous cohorts: self-referred participants, healthcare worker referred, and those referred by a lung cancer screening program if they were still actively smoking at the time of first contact. Baseline, covariates (sociodemographic information, smoking history, and history of mental health disorder) and quit intentions (stage of change, readiness for change, previous use of quit programs, and previous quit attempts) were compared among the three cohorts. Our primary outcome was defined as self-reported 30-day abstinence rates at 6 months. Multivariable logistic regression was used to identify whether group assignment was associated with higher quit rates. Results: Participants referred by a lung cancer screening program had low quit rates (12%, 95% CI: 5-19) at six months despite the use of phone counselling. Compared to patients who were self-referred to the smoking cessation phone helpline, individuals referred by a lung cancer screening program were much less likely to quit (adjusted OR 0.37; 95% CI: 0.17-0.8), whereas those referred by healthcare workers were twice as likely to quit (adjusted OR 2.16 (1.3-3.58)) even after adjustment for differences in smoking intensity and quit intentions. Conclusions: Phone counselling alone has very limited benefit in a lung cancer screening program. Participants differ significantly from those who are otherwise referred by healthcare workers. This study underlines the importance of a dedicated and personalized tobacco treatment program within every lung cancer screening program. The program should incorporate best practices and encourage treatment regardless of readiness to quit.

SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria.

Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca2+) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca2+-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.

An Audit of CT Chest Reports and Their Potential Impact on the Workup of Patients with Suspected Lung Cancer.

Background: Quality gaps exist in the diagnostic evaluation of lung cancer patients. The initial CT chest guides the workup of patients with suspected lung cancer. We sought to determine how frequently CT reports provided guideline-concordant recommendations with regard to additional imaging studies and/or invasive diagnostic procedures. Methods. This was a retrospective study. The records of patients referred for investigation of suspected lung cancer between January 1, 2015, and June 30, 2016, were reviewed. Patients with confirmed lung cancer, for whom CT scan images and reports were available, are included. CT reports were reviewed, with attention to additional imaging studies and/or invasive diagnostic procedures suggested. These recommendations were examined against current guidelines for lung cancer diagnosis and staging, based on suspected disease stage. Results: One hundred forty-six patients are included in the analysis. Most patients were diagnosed with non-small-cell lung cancer (NSCLC), and 63% had advanced disease (stages III and IV). Only 12% of CT reports contained guideline-concordant recommendations for additional imaging studies, with PET scan suggested in only 6% of reports. Potential invasive diagnostic procedures were suggested in one fifth of CT reports, and only 58% of these recommendations were in keeping with current guidelines. In particular, transthoracic needle aspiration (TTNA) was suggested in 26% of patients despite advanced stage disease. Conclusion: Guideline-concordant recommendations for investigation of suspected lung cancer are rarely available on CT reports. This is true with respect to both imaging studies and invasive diagnostic procedures. Incorporation of more evidence-based suggestions may reduce quality gaps in lung cancer diagnosis and staging.

Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience.

OBJECTIVE: For the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs. METHODS: This retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection. RESULTS: Fifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARS-CoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen's k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively. CONCLUSIONS: BAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high.

Overuse of small chest drains for pleural effusions: a retrospective practice review.

PURPOSE: Small-bore drains (≤ 16 Fr) are used in many centers to manage all pleural effusions. The goal of this study was to determine the proportion of avoidable chest drains and associated complications when a strategy of routine chest drain insertion is in place. DESIGN/METHODOLOGY/APPROACH: We retrospectively reviewed consecutive pleural procedures performed in the Radiology Department of the McGill University Health Centre over one year (August 2015-July 2016). Drain insertion was the default drainage strategy. An interdisciplinary workgroup established criteria for drain insertion, namely: pneumothorax, pleural infection (confirmed/highly suspected), massive effusion (more than 2/3 of hemithorax with severe dyspnea /hypoxemia), effusions in ventilated patients and hemothorax. Drains inserted without any of these criteria were deemed potentially avoidable. FINDINGS: A total of 288 procedures performed in 205 patients were reviewed: 249 (86.5%) drain insertions and 39 (13.5%) thoracenteses. Out of 249 chest drains, 113 (45.4%) were placed in the absence of drain insertion criteria and were deemed potentially avoidable. Of those, 33.6% were inserted for malignant effusions (without subsequent pleurodesis) and 34.5% for transudative effusions (median drainage duration of 2 and 4 days, respectively). Major complications were seen in 21.5% of all procedures. Pneumothorax requiring intervention (2.1%), bleeding (0.7%) and organ puncture or drain misplacement (2%) only occurred with drain insertion. Narcotics were prescribed more frequently following drain insertion vs. thoracentesis (27.1% vs. 9.1%, p = 0.03). ORIGINALITY/VALUE: Routine use of chest drains for pleural effusions leads to avoidable drain insertions in a large proportion of cases and causes unnecessary harms.

Real-World Outcomes of Patients With Advanced Non-small Cell Lung Cancer Treated With Anti-PD1 Therapy on the Basis of PD-L1 Results in EBUS-TBNA vs Histological Specimens.

BACKGROUND: Programmed death-ligand 1 (PD-L1) testing is feasible in most specimens acquired using endobronchial ultrasound-guided needle aspiration (EBUS-TBNA). RESEARCH QUESTION: Are the outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) on the basis of PD-L1 expression in EBUS-TBNA samples significantly different from those of patients who are treated on the basis of PD-L1 expression in histological samples? STUDY DESIGN AND METHODS: Patients treated with pembrolizumab or nivolumab between June 2016 and 2019 were included. Patient characteristics, PD-L1 expression, line of treatment, response (Response Evaluation Criteria in Solid Tumors [RECIST] criteria), and vital status (May 14, 2020) were recorded. Progression-free survival (PFS) and overall survival (OS) were assessed, and hazard ratios (HR) estimated. RESULTS: A total of 145 patients were treated with pembrolizumab or nivolumab on the basis of PD-L1 expression in EBUS-TBNA (31.7%) or histological (68.3%) samples. Most had metastatic disease, with a predominance of adenocarcinomas (64.1%). First-line pembrolizumab was administered to 61 patients with tumor proportion score ≥50% in EBUS-TBNA (n = 16) or histology samples (n = 45). Median OS and PFS of patients who received first-line pembrolizumab on the basis of PD-L1 results in EBUS-TBNA vs histology samples were not significantly different (OS 25.8 months vs not reached, respectively; HR, 0.82 [95% CI, 0.34-1.95], P = .651). Similarly, the median OS and PFS of patients who received subsequent lines of treatment on the basis of PD-L1 results in EBUS-TBNA vs histological samples were not significantly different (including after adjustment for PD-L1 expression). INTERPRETATION: These findings suggest that PD-L1 results in EBUS-TBNA samples can guide ICI therapy, with treatment outcomes being comparable to those of patients in whom PD-L1 expression was assessed in histological specimens.

Bronchoscopic tissue yield for advanced molecular testing: are we getting enough?

The treatment of advanced lung cancer has become increasingly personalized over the past decade as a result of the improved understanding of tumor molecular biology and anti-tumor immunity. An adequate tumor sample is central to targetable mutation analysis, and immunologic profiling. The majority of lung cancer patients currently present at an advanced disease stage, so that diagnosis and staging are largely based on small biopsy and cytology specimens. Flexible bronchoscopy techniques play a prominent role in the acquisition of these diagnostic specimens. This narrative review summarizes the available evidence with regards to the role of various conventional and advanced flexible bronchoscopy techniques in acquiring sufficient tissue for mutation analysis and programmed death-ligand 1 (PD-L1) testing.